This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moriyama, K. Articles by Arakawa, K. Search for Related Content PubMed PubMed Citation Articles by Moriyama, K. Articles by Arakawa, K.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:1416-1423.)
© 1996 American Heart Association, Inc.

Articles

A Cysteine-Containing Truncated Apo A-I Variant Associated With HDL Deficiency

Kengo Moriyama; Jun Sasaki; Yoichi Takada; Akira Matsunaga; Jun Fukui; John J. Albers; Kikuo Arakawa

the Department of Internal Medicine (K.M., J.S., Y.T., A.M., K.A.), Fukuoka (Japan) University, School of Medicine; Sasebo General Hospital (J.F.), Nagasaki, Japan; and the Department of Medicine (J.J.A.), University of Washington, Northwest Lipid Research Laboratories, Seattle.

Correspondence to Jun Sasaki, MD, Department of Internal Medicine, Fukuoka University, School of Medicine, 45-1, 7-chome Nanakuma, Jonan-Ku, Fukuoka, 814-80, Japan.

We identified a 50-year-old Japanese woman with a novel mutation in the apolipoprotein (apo) A-I gene causing high-density lipoprotein (HDL) deficiency. The patient had extremely low HDL cholesterol and apo A-I levels (0.14 mmol/L and 0.8 mg/dL, respectively) but no evidence of coronary heart disease. However, she had bilateral xanthomas of the Achilles tendon, elbow, and knee joint as well as corneal opacities. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis of serum followed by immunoblotting revealed that the patient's apo A-I had a lower molecular weight (24 000) than normal apo A-I. A partial gene duplication encompassing 23 nucleotides was found by DNA sequence analysis, resulting in a tandem repeat of bases 333 to 355 from the 5' end of exon 4. This tandem repeat caused a frameshift mutation with premature termination after amino acid 207. The frameshift gives rise to a predicted protein sequence that contains two cysteines. We designated this mutant as apo A-I_Sasebo. Apo A-I_Sasebo formed heterodimers with apo A-II and apo E in the patient's plasma and was associated with both the low-density lipoprotein and HDL fractions. The patient's cholesterol esterification rate and lecithin-cholesterol acyltransferase activity were reduced to about 30% of normal, although specific enzyme activity was unaffected, suggesting that it remained functionally normal. In addition, cholesteryl ester transfer activity was reduced to about half of normal. Thus, apo A-I_Sasebo was associated with complex derangements of lipoprotein metabolism.

Key Words: genetics • lipoproteins • apo E • apo A-II • atherosclerosis

This article has been cited by other articles:

				G. K. Hovingh, A. Brownlie, R. J. Bisoendial, M. P. Dube, J. H.M. Levels, W. Petersen, R. P.F. Dullaart, E. S.G. Stroes, A. H. Zwinderman, E. de Groot, et al. A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1429 - 1435. [Abstract] [Full Text] [PDF]

				S. Altilia, L. Pisciotta, R. Garuti, P. Tarugi, A. Cantafora, L. Calabresi, J. Tagliabue, S. Maccari, F. Bernini, I. Zanotti, et al. Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 +5G>C mutation in ABCA1 gene J. Lipid Res., February 1, 2003; 44(2): 254 - 264. [Abstract] [Full Text] [PDF]

				T. Oka, S. Yamashita, T. Kujiraoka, M. Ito, M. Nagano, Y. Sagehashi, T. Egashira, M. N. Nanjee, K.-i. Hirano, N. E. Miller, et al. Distribution of human plasma PLTP mass and activity in hypo- and hyperalphalipoproteinemia J. Lipid Res., August 1, 2002; 43(8): 1236 - 1243. [Abstract] [Full Text] [PDF]

				H. Han, J. Sasaki, A. Matsunaga, H. Hakamata, W. Huang, M. Ageta, T. Taguchi, T. Koga, M. Kugi, S. Horiuchi, et al. A Novel Mutant, ApoA-I Nichinan (Glu235->0), Is Associated With Low HDL Cholesterol Levels and Decreased Cholesterol Efflux From Cells Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1447 - 1455. [Abstract] [Full Text] [PDF]

				A. Matsunaga, J. Sasaki, H. Han, W. Huang, M. Kugi, T. Koga, S. Ichiki, T. Shinkawa, and K. Arakawa Compound Heterozygosity for an Apolipoprotein A1 Gene Promoter Mutation and a Structural Nonsense Mutation With Apolipoprotein A1 Deficiency Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 348 - 355. [Abstract] [Full Text] [PDF]

				W. Huang, J. Sasaki, A. Matsunaga, H. Nanimatsu, K. Moriyama, H. Han, M. Kugi, T. Koga, K. Yamaguchi, and K. Arakawa A Novel Homozygous Missense Mutation in the Apo A-I Gene With Apo A-I Deficiency Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 389 - 396. [Abstract] [Full Text] [PDF]